Proteins are composed of a series of amino acid residues. There are 20 known naturally occurring amino acids. The three-dimensional structure of a protein is typically composed of a series of folded regions. Current research has focused on protein structural determination because three dimensional protein structure is important for all human bodily functions.
Many proteins are globular and form in an aqueous environment. These globular proteins are composed of hydrophobic amino acids that avoid water, and hydrophilic amino acids that are attracted to water. When these proteins fold, the hydrophobic amino acids are predominantly arranged in the non-aqueous center of the protein molecule and the hydrophilic amino acids are arranged on the aqueous protein surface. A protein formed in this manner will have a hydrophobic core and a hydrophilic exterior. In addition to this inside-to-outside radial distribution of hydrophobic and hydrophilic amino acids, there is a gradient of the hydrophobicity of amino acids across the linear extent of the protein. This gradient is important since, in many instances, it points to local regions that are involved in protein function. Many of these protein functional regions consist of a predominance of hydrophilic amino acids. In the binding to lipid bilayers these regions may consist of hydrophobic amino acid residues.
The profile of the spatial distribution of hydrophobic and hydrophilic amino acids from the protein interior to exterior has been performed previously, in B. D. Silverman, Hydrophobic Moments of Protein Structures: Spatially Profiling the Distribution, 98 PROC. NATL. ACAD. SCI. 4996-5001 (2001). Previous methods involved the determination of a helical hydrophobic moment that provides a measure of the amphiphilicty of a segment of a secondary protein structure. See for example, D. Eisenberg et al., The Helical Hydrophobic Moment: a Measure of the Amphiphilicity of a Helix, 299 NATURE 371-74 (1982); D. Eisenberg et al., Analysis of Membrane Protein Sequences With the Hydrophobic Moment Plot, 179 J. MOL. BIOL. 125-142 (1984); H. J. Pownall et al., Helical Amphipathic Moment: Application to Plasma Lipoproteins, 159 FEBS 17-23 (1983); I. Tsigelny et al., Mechanism of Action of Chromogranin A on Catecholamine Release Molecular Modeling of the Catestatin Region Reveals a β-strand/loop/β-strand Structure Secured by Hydrophobic Interactions and Predictive of Activity, 77 REGULATORY PEPTIDES 43-53 (1998); J. P. Pardo et al., An Alternative Model for the Transmembrane Segments of the Yeast H+-ATPase, 15 YEAST 1585-93 (1999); P. W. Mobley, Membrane Interactions of the Synthetic N-terminal Peptide of HIV-1 gp41 and its Structural Analogs, 1418 BIOCHIMICA ET BIOPHYSICA ACTA, 1-18 (1999); L. Thong et al., Flexible Programs for the Prediction of Average Amphiphilicity of Multiply Aligned Homologous Proteins: Application to Integral Membrane Transport Proteins, 16 MOLECULAR MEMBRANE BIOLOGY 173-79 (1999); X. Gallet et al., A Fast Method to Predict Protein Interaction Sites from Sequences, 302 J. MOL. BIOL. 917-926 (2000); D. A. Phoenix et al., The Hydrophobic Moment and its Use in the Classification of Amphiphilic Structures (Review), 19 MOLECULAR MEMBRANE BIOLOGY 1-10 (2002).
While determination of the hydrophobic moments of secondary structures are useful, it is desirable to have measurements pertaining to the entire protein structure. These measurements would yield information useful in protein structure classification and functional region determination.